Topiramate affords neuroprotection in diabetic neuropathy model via downregulating spinal GFAP/inflammatory burden and improving neurofilament production

Abstract

The current study aimed to test the neuroprotective action of topiramate in mouse peripheral diabetic neuropathy (DN) and explored some mechanisms underlying this action. Mice were assigned as vehicle group, DN group, DN + topiramate 10-mg/kg and DN + topiramate 30-mg/kg. Mice were tested for allodynia and hyperalgesia and then spinal cord and sciatic nerves specimens were examined microscopically and neurofilament heavy chain (NEFH) immunostaining was performed. Results indicated that DN mice had lower the hotplate latency time (0.46-fold of latency to licking) and lower von-Frey test pain threshold (0.6-fold of filament size) while treatment with topiramate increased these values significantly. Sciatic nerves from DN control mice showed axonal degeneration while spinal cords showed elevated GFAP (5.6-fold) and inflammatory cytokines (∼3- to 4-fold) but lower plasticity as indicated by GAP-43 (0.25-fold). Topiramate produced neuroprotection and suppressed spinal cord GFAP/inflammation but enhanced GAP-43. This study reinforces topiramate as neuroprotection and explained some mechanisms included in alleviating neuropathy.

Keywords:

• GFAP
• mouse diabetic neuropathy
• neurofilament
• inflammatory burden
• sciatic nerve
• spinal cord

Acknowledgments

The authors are thankful to Tabuk Pharmaceuticals for kindly providing topiramate. Authors are thankful to Dr. Khaled Elbayoumi, Department of Anatomy and Embryology at Faculty of Medicine, Mansoura University for help in performing the ETM scan.

Author contributions

Conceptualization, Mohammed Attia and Sawsan Zaitone; Data curation, Nema S. Abu-Maziad; Formal analysis, Howaida Ali and Sawsan Zaitone; Investigation, Nema S. Abu-Maziad and Sawsan Zaitone; Methodology, Nema S. Abu-Maziad, Taghrid El-Abaseri, Faten Abbas, Dalia Ibrahim and Sawsan Zaitone; Project administration, Sawsan Zaitone; Resources, Mohammed Attia, Nema S. Abu-Maziad, Shymaa Bilay, Taghrid El-Abaseri, Howaida Ali, Faten Abbas, Dalia Ibrahim, Mohamed Eladl, Noura Osman, Abdullah Hashish, Asma Alshahrani and Abir Mohamed; Software, Mohamed Eladl, Noura Osman and Abdullah Hashish; Visualization, Mohammed Attia, Nema S. Abu-Maziad, Shymaa Bilay, Taghrid El-Abaseri, Howaida Ali, Faten Abbas, Dalia Ibrahim, Mohamed Eladl, Noura Osman, Abdullah Hashish, Asma Alshahrani, Abir Mohamed and Sawsan Zaitone; Writing – original draft, Mohammed Attia, Nema S. Abu-Maziad, Faten Abbas and Dalia Ibrahim; Writing – review & editing, Shymaa Bilay, Taghrid El-Abaseri, Howaida Ali, Mohamed Eladl, Noura Osman, Abdullah Hashish, Asma Alshahrani, Abir Mohamed and Sawsan Zaitone.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data are available from the authors upon request.

Additional information

Funding

Self.